Specific T-Cell Subsets Can Predict the Efficacy of Anti-TNF Treatment in Inflammatory Bowel Diseases

Sonja Dulic,Ágnes Milassin,Tamás Molnár,Mariann Rutka,László Kovács,Klaudia Farkas,Attila Balog,Florentina Sava,Gergely Toldi

doi:10.1007/s00005-020-00575-5

Sonja Dulic, Ágnes Milassin + Show 7 more

Open Access

https://doi.org/10.1007/s00005-020-00575-5

Copy DOI

Abstract

The effect of TNF-blockers on T-lymphocyte subsets is largely unknown in inflammatory bowel diseases (IBDs). The aim of the present study was to analyze the prevalence of T-cell subtypes and their correlation to therapeutic response. Sixty-eight patients with Crohn’s disease (CD), 46 with ulcerative colitis (UC) were enrolled. (1) The clinical course was followed after the initiation of TNF-blockers (prospective study). (2) The immunophenotype was also compared between long-term anti-TNF treated-responders and non-responders (cross-sectional study). The results were compared with those of therapy-naïve patients with active disease and those in remission with non-biological immunosuppressive therapy, and with healthy controls. Fourteen subtypes of peripheral blood T cells were measured with flow cytometry. The prevalence of Th2 and Th17 cells, of HLA-DR- and CD69-positive CD4 and CD8 cells, was higher, whereas the percentage of CD45RA-positive CD4 and CD8 cells was lower in both IBDs than in controls. CD8CD69 cell frequency was lower in remission, and decreased during anti-TNF therapy in CD responders. CD8CD45RO memory cells had higher prevalence in UC non-responders than in those starting anti-TNF. CD4CD45RO percentage < 49.05 at the initiation of TNF-blockers was predictive of a subsequent therapeutic response in CD, and Th2 and Th17 prevalence correlated with the duration of remission on TNF-blockers in UC. This study provided a detailed description of the T-cell composition in IBDs. CD8CD69 prevalence may be an activity marker in CD, and CD4CD45RO, Th2 and Th17 levels could be predictive for a therapeutic response to anti-TNF.

Highlights

Inflammatory bowel diseases (IBDs) are chronic immunemediated diseases involving the gastrointestinal tract and are frequently associated with extra-intestinal manifestations
CD4CD45RO percentage < 49.05 at the initiation of TNF-blockers was predictive of a subsequent therapeutic response in Crohn’s disease (CD), and Th2 and Th17 prevalence correlated with the duration of remission on TNF-blockers in ulcerative colitis (UC)
Patient subgroups for both diagnoses were similar in terms of age, disease duration, frequency of extraintestinal manifestations, surgical interventions necessitated by IBD, type of anti-TNF, other therapies ever used, or smoking status

Summary

Introduction

Inflammatory bowel diseases (IBDs) are chronic immunemediated diseases involving the gastrointestinal tract and are frequently associated with extra-intestinal manifestations. The pathogenesis of Department of Rheumatology and Immunology, Faculty of Medicine, Albert Szent‐Györgyi Health Center, University of Szeged, Kálvária sgt. First Department of Medicine, Faculty of Medicine, Albert Szent‐Györgyi Health Center, University of Szeged, Szeged, Hungary. IBD is still not clearly understood despite intensive research, but an inappropriate mucosal immune response to gut microflora is a well-recognized phenomenon in the pathogenesis (Ogura et al 2001; Lamas et al 2016). Both the innate and the adaptive immune system play important roles in the intestinal inflammation. There is an established difference between the two major representative IBD subgroups as CD is associated

Objectives

Methods

Results

Conclusion